Comparison of Toxicity between Propylene Glycol (PG)-Free Melphalan with PG-Melphalan for Autologous Hematopoietic Cell Transplantation (AHCT) in Patients with Multiple Myeloma (MM)

Abstract

Introduction High-dose melphalan (Mel) conditioning before AHCT has been standard in MM. The lyophilized Mel formulation has inadequate solubility and stability after reconstitution, and propylene glycol (PG) which is used to improve solubility, is associated with toxicity. A PG-free Mel preparation, Evomela, uses captisol as a solubilizing agent and in a phase IIb study showed acceptable safety profile, comparable efficacy and was FDA approved as a conditioning regimen for AHCT. There is limited evidence directly comparing toxicity and outcomes between the two Mel formulations used as conditioning for AHCT in MM. Objective Compare early post-AHCT toxicity and outcomes in MM patients receiving conditioning with PG-Mel vs. PG-free Mel. Methods This is a single-center retrospective study analyzing outcomes in a cohort of consecutive MM patients receiving AHCT using Mel conditioning between 01/2015 and 01/2018. Our center switched from using PG-Mel to PG-free Mel in 11/2016. The cohort was divided into 2 groups based on Mel formulation (PG-Mel vs. PG-free Mel); patients enrolled immediately prior to this date and immediately after formed 2 groups. The primary endpoint was toxicities in 30 days of AHCT. Secondary endpoints included engraftment, early infections, day 100 responses and mortality. Covariate balancing weights were computed using inverse propensity scores based on age, KPS, ISS, HCT-CI, cytogenetic risk, lines of therapy pre-AHCT and Mel dose. Weighted analysis was performed to estimate the average treatment effect of PG-Mel vs. PG-free Mel on outcomes. Results Of 294 AHCT patients, 162 received PG-Mel and 132 received PG-free Mel conditioning. PG-free Mel patients were older and had lower KPS (Figure 1). In univariate analysis, PG-free Mel was associated with faster neutrophil recovery (12 vs. 13 days, p Conclusion Preliminary analysis suggests PG-free Mel conditioning allows modest improvement in time to engraftment and risk of severe infections, compared to PG-Mel. Organ toxicity profile and 100-day mortality are comparable.